Two ongoing phase II studies investigate new types of chemotherapy in patients with primary and metastatic brain tumors refractory to surgery, radiation and standard chemotherapy. The effect of DMSO in opening reversibly the blood-brain barrier for chemotherapeutic agents is being evaluated. Patients with indwelling Ommaya reservoirs undergo repeated CSF sampling to determine the CSF pharmacokinetics of simultaneously administered chemotherapy. Twelve patients were studied with DMSO plus cyclophosphamide. The DMSO did not alter any aspect of cyclophosphamide or alkylating activity disposition. Six patients have been treated with DMSO plus Adriamycin. Adriamycin aglycones were increased in the CSF, presumably related to either DMSO or the tumors themselves. Another study looks at the new agent AZQ (aziridinylbenzoquinone). Thirteen patients with glioblastomas have been entered. One has had a partial response, 1 is stable, 7 have failed to respond and 4 are inevaluable. In addition, 5 patients with tumors metastatic to brain have been entered. One of these has had a response, 2 are stable, 1 failed and 1 is inevaluable.